The life expectancy of adults receiving antiretroviral therapy (ART) has been increasing progressively. By 2015 one-half of HIV+ people in the U.S. will be over age 50, and this number is expected to continue to rise. While there has been a growing interest in aging with HIV, there is a dearth of research on successful aging with HIV. We define successful aging as a multi-dimensional construct with physical, cognitive, and psychosocial domains, with the downstream outcome being self-perceived successful aging. The proposed study will be the first large-scale investigation examining the relationship of positive psychological factors such as resilience, hardiness, optimism, and social engagement along with laboratory-based systemic markers of biological aging and HIV disease severity to the different domains of successful aging in HIV+ individuals as compared to well- matched Non-HIV-infected Comparison subjects (NCs). Subjects will include 120 HIV+ adults and 90 NCs aged 36-65 years. The biomarkers will include: telomere length, F2-isoprostanes, inflammatory markers (high- sensitivity C-reactive protein, IL-6, d-dimer, TNF-alpha, CCL2, d-dimer and sCD14), insulin resistance, and allostatic load, and, among HIV+ individuals, indicators of HIV disease severity (plasma HIV viral load, CD4+ T-cell count, AIDS/nonAIDS). Participants in each decade (36-45, 46-55, 56-65) will be evaluated using a structured Multi-cohort Longitudinal Design (sMLD), with balanced recruitment providing 40 HIV+ and 30 HIV- subjects per decade. The sMLD enables separation of cohort effects from developmental (within-subject) aging effects, allowing us to estimate aging trajectories across the entire age range of 36-65 years. Subjects will be followed for up to 4 years, with in-person bi-annual visits for detailed assessments, and evaluated with follow- up telephone interviews and mail surveys in the years in which they are not seen in person. We will examine the longitudinal trajectories of clinical outcome measures and positive psychological factors as well as biomarkers of aging and HIV disease, and compare them to those in NC subjects. Our first aim is to determine whether and how trajectories of successful aging differ between HIV+ and NC groups. We will also identify predictors of successful aging trajectories in HIV+ and NC groups. This project is related to NIMH Strategic Objective #2: charting illness trajectories to determine when, where, and how to intervene with HIV+ individuals. This study is novel in its focus on multi-dimensional characterization and recognition of predictors of successful aging in HIV+ adults as well as the use of advanced statistical methodology that allows for the distinction of cohort and developmental aging effects. We anticipate that successful aging trajectories will differ between HIV+ and NC groups suggesting that successful aging paradigms established in non-HIV-infected cannot be simply be generalized to HIV-infected persons. Understanding potentially malleable protective versus risk factors at an individual level may lead to development of new interventions aimed at increasing the likelihood of successful aging among people living with HIV.